Evidence for structural and functional abnormality in the subgenual anterior cingulate cortex in major depressive disorder.

BACKGROUND: The subgenual anterior cingulate cortex (sgACC) is considered to be an important site of abnormality in major depressive disorder. However, structural alterations in this region have not been a consistent finding and functional imaging studies have also implicated additional areas. METHOD: A total of 32 patients with major depressive disorder, currently depressed, and 64 controls underwent structural imaging with MRI. Also, 26 patients and 52 controls were examined using functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Structural and functional changes were evaluated using whole-brain, voxel-based methods. RESULTS: The depressed patients showed volume reductions in the sgACC and orbitofrontal cortex bilaterally, plus in both temporal poles and the hippocampus/parahippocampal gyrus on the left. Functional imaging revealed task-related hypo-activation in the left lateral prefrontal cortex and other regions, as well as failure of deactivation in a subcallosal medial frontal cortical area which included the sgACC. CONCLUSIONS: Whole-brain, voxel-based analysis finds evidence of both structural and functional abnormality in the sgACC in major depressive disorder. The fact that the functional changes in this area took the form of failure of deactivation adds to previous findings of default mode network dysfunction in the disorder.

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects.

The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.

Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease relates to visuomotor performance and CAG number.

PURPOSE: To investigate grey matter volumes on magnetic resonance imaging (MRI) in preclinical Huntington's disease (HD), and their relationship to neuropsychology and CAG number. MATERIAL AND METHODS: Twenty preclinical HD carriers and 21 healthy controls matched for age, sex, and educational level were included in this study. Clinical (UHDRS), and detailed neuropsychological assessments, and 3D IR SPGR axial MR acquisition. Calculation of global, segmented (SIENAX), and focal (voxel based morphometry, VBM) grey matter volumes was carried out. An analysis of variance (ANOVA) and a general linear model for VBM analysis were used to compare preclinical HD carriers and controls. Small volume correction was used, and clusters at p<0.05 were considered significant. Correlation analysis (VBM) with neuropsychology, and CAG number was also performed. RESULTS: Preclinical HD carriers showed, compared to controls, smaller global volumes of the brain (1279+/-6 vs. 1331+/-46, p=0.003), total (666+/-48 vs. 698+/-34, p=0.020) and cortical grey matter (551+/-44 vs. 577+/-32, p=0.035). When compared to the controls, preclinical carriers showed focal volume losses, which were more prominent in the left prefrontal cortex, cerebellum, and right posterior temporal cortex. Preclinical HD performed slower in a visuomotor integration task, the 15-Objects test, than controls (t (1,25.02)=3.69; p=0.001: pre-HD: 69.55+/-28.86; controls: 45.79+/-8.38). A correlation was found between volume loss in the prefrontal cortex, visuomotor performance, and CAG number. CONCLUSION: Preclinical HD carriers show grey matter volume reduction involving the prefrontal cortex, which relates to the visuomotor performance and CAG number. This suggests that regionally selective neuronal loss/dysfunction occurs prior to the clinical onset of symptoms.

Naming is associated with left temporal pole metabolite levels in neurodegenerative diseases.

AIM: To investigate the relationship between performance in language tests and levels of brain metabolites in two selected left temporal lobe regions. METHODS: Ninety-five subjects were included: 26 controls, 30 amnestic mild cognitive impairment subjects, 27 Alzheimer's disease and 12 frontotemporal lobar degeneration (FTLD) patients. Language was assessed by a naming test: Boston Naming Test (BNT) and by a semantic verbal fluency test. Other cognitive functions: verbal and visual memory, visual perception, attention and executive function, and praxis were also assessed. Single voxel magnetic resonance spectroscopy was obtained in the left temporal pole (L-TPOLE), and in the left posterior temporoparietal region (L-TPAR). RESULTS: BNT scores were significantly associated with N-acetylaspartate/creatine ratios (r = 0.45; p < 0.001) and choline/creatine ratios (r = 0.33; p < 0.005) in the L-TPOLE. No significant associations were found between BNT and metabolite levels in the L-TPAR. No significant associations were found between the semantic verbal fluency test and other cognitive tests and metabolite levels either in the L-TPOLE or in the L-TPAR. CONCLUSION: Naming performance is related to metabolite levels in the anterior L-TPOLE.

Cortical brain metabolism as measured by proton spectroscopy is related to memory performance in patients with amnestic mild cognitive impairment and Alzheimer's disease.

AIMS: To investigate the relationship between verbal memory performance and brain metabolism as determined by proton spectroscopy ((1)H-MRS) in selected cortical brain regions. To characterize metabolite abnormalities across the continuum of degenerative disease from mild impairment to dementia. METHODS: 27 controls, 27 amnestic mild cognitive impairment (aMCI) patients and 35 Alzheimer's disease (AD) patients. Verbal memory was assessed with the Text Memory Test, the Wordlist Learning Test (WL-Learning Test), and with a memory screening test, the Memory Alteration Test (M@T). Single-voxel (1)H-MRS was obtained in the posterior cingulate (P-CING), left temporal pole (L-TPOLE) and left posterior temporoparietal region (L-TPAR). RESULTS: WL-Learning Test scores were inversely associated with myoinositol/creatine ratios (mI/Cr) in the L-TPAR (r = -0.404, p < 0.002). Negative associations were also observed between M@T global scores and mI/Cr in the P-CING (r = -0.42; p < 0.001), L-TPOLE (r = -0.34; p < 0.005) and L-TPAR (r = -0.46; p < 0.001). A positive association was found between M@T scores and N-acetylaspartate concentrations in the P-CING (r = 0.33; p < 0.003). CONCLUSION: Verbal learning performance is related to metabolic changes in cortical brain regions known to be involved in the neurodegenerative process of aMCI and AD.

Decreased frontal choline and neuropsychological performance in preclinical Huntington disease.

OBJECTIVES: To study metabolic brain changes in preclinical carriers of Huntington disease (PreHD) using proton magnetic resonance spectroscopy (1H-MRS) and to examine their relationship to neuropsychological performance. METHODS: Seventeen subjects with PreHD and 17 controls, matched for age and education, were studied. Frontal cortex and basal ganglia 1H-MRS, and a detailed neuropsychological battery, including visuomotor integration and speed, and memory, frontal, and visuospatial tests were performed. Statistical analysis included Student t-test and Pearson correlations (significance p < 0.05). RESULTS: Frontal choline-containing compounds (CHO) were decreased in PreHD [t (32) = -2.834, p = 0.008]. Subjects with PreHD performed worse than controls in the 15-Objects test [t (32) = 4.077, p = 0.000], Luria motor alternances [t (32) = -2.094, p = 0.044], and Symbol Digit tests [t (32) = -2.136, p = 0.040]. Decreased frontal CHO in PreHD correlated to slowing in visuomotor tasks (the 15-Objects test: r = -0.60, p = 0.000, and the Symbol Digit: r = 0.37, p = 0.047). CONCLUSION: As choline-containing compounds relate to membrane turnover, membrane dysfunction antedating neuronal death is suggested to occur in the frontal cortex in preclinical carriers of Huntington disease. This dysfunction may be responsible for some of the neuropsychological deficits observed.